[Clinical pharmacokinetics of navelbine after oral administration, in vitro metabolism and interindividual variability].
Navelbine (NVB) (5'-noranhydrovinblastine) is a new semi-synthetic vincaalkaloid (VA) exhibiting a high affinity for tubulin and considerable anticancer activity in patients. A better hematologic tolerance and a weak neurotoxicity have been reported for this drug as compared to other VA. Moreover, NVB presents a relatively high bioavailability and a good digestive tolerance, thus offering original perspectives for the treatment of ambulatory cancer patients. A clinical pharmacokinetic study of NVB was carried out on 12 patients after oral administration of the drug. The pharmacokinetic parameters were similar to those of intravenous administration and also showed a high interindividual variability. Studies on the in vitro metabolism of NVB using hepatic microsomal fractions from 22 different donors demonstrated the formation of 3 metabolites. The biotransformation rate quantitatively varies from one human liver specimen to another, a fact which could be, in part, at the origin of the interindividual variability of the therapeutic response.
Sahnoun
Z
Z
INSERM U 278, faculté de pharmacie, institut Paoli-Calmettes, Marseilles, France.
Zhou
X J
XJ
Bore
P
P
Monjanel
S
S
Favre
R
R
Durand
A
A
Rahmani
R
R
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism; D010039:Otorhinolaryngologic Neoplasms / Q000188:drug therapy*; D011863:Radioimmunoassay; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D000077235:Vinorelbine
Pharmacocinétique clinique de la navelbine après administration orale métabolisme in vitro et variabilité interindividuelle.